The proposed studies have two long-term goals: (1) to understand the molecular signals that initiate sexually dimorphic development of the brain, and lead to sex differences in behavior and (2) to understand the effects of Y chromosome action on the brain. The proposal seeks to determine when and where Y chromosome genes are expressed in brain, and how they act. The sites and times of neural expression of Y chromosome genes will be determined. To establish correlations between Y chromosome expression in brain and the Y gene effects on behavior, Y chromosome gene expression in the brain will be compared in several dyadic comparisons of mouse strains that differ only in their Y chromosome and show differences in behavior attributed to the action of Y chromosome genes. These studies will identify candidate Y genes that are responsible for the Y-induced differences in behavior. The role of these candidate genes will be tested by measuring the reproductive and aggressive behavior of mouse strains that differ in level of expression of only a single Y gene. The reciprocal influence of Y genes and gonadal androgens will be tested by measuring the interaction of androgens and Y genes on behavior. The proposed research will contribute significantly to an understanding of the principles of sexual differentiation of the brain. At issue are the molecular mechanisms by which male and female brains differ, which is relevant to the biological basis of abnormalities of sexual differentiation, and to the explanation of sex differences in neurological and psychiatric disease (e.g., Alzheimer's Disease and Multiple Sclerosis). The proposed studies will also help explain genetic effects of sex chromosome aneuploidy (Klinefelter Syndrome 47,XXY, and 47,XYY) on behavior and will shed light on the forces that control reproductive behavior, aggressive behavior and hyperaggression.